Spatial single-cell protein landscape reveals vimentinhigh macrophages as immune-suppressive in the microenvironment of hepatocellular carcinoma

Tumor microenvironment heterogeneity in hepatocellular carcinoma (HCC) on a spatial single-cell resolution is unclear. Here, we conducted co-detection by indexing to profile the spatial heterogeneity of 401 HCC samples with 36 biomarkers. By parsing the spatial tumor ecosystem of liver cancer, we identified spatial patterns with distinct prognosis and genomic and molecular features, and unveiled the progressive role of vimentin (VIM)high macrophages. Integration analysis with eight independent cohorts demonstrated that the spatial co-occurrence of VIMhigh macrophages and regulatory T cells promotes tumor progression and favors immunotherapy. Functional studies further demonstrated that VIMhigh macrophages enhance the immune-suppressive activity of regulatory T cells by mechanistically increasing the secretion of interleukin-1β. Our data provide deep insights into the heterogeneity of tumor microenvironment architecture and unveil the critical role of VIMhigh macrophages during HCC progression, which holds potential for personalized cancer prevention and drug discovery and reinforces the need to resolve spatial-informed features for cancer treatment. Qui et al. perform co-detection by indexing profiling of 401 hepatocellular carcinoma patient samples and identify a role for vimentinhigh macrophages in instructing an immune-suppressive microenvironment by enhancing the suppressive activity of regulatory T cells via interleukin-1β.